2014 Fiscal Year Final Research Report
Study on homeostatic regulation by glucocorticoid
| Project/Area Number |
24390236
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SHIMIZU Noriaki 東京大学, 医科学研究所, 特任研究員 (30396890)
YOSHIKAWA Noritada 東京大学, 医科学研究所, 助教 (70396878)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | ホルモン / ステロイド / 転写因子 / 代謝 / 副腎皮質 / 遺伝子発現 / 副作用 |
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| Outline of Final Research Achievements |
Skeletal muscle has a pleiotropic role in organismal energy metabolism by storing protein as an energy source, or by excreting endocrine hormones. Muscle proteolysis is tightly controlled by the hypothalamus-pituitary-adrenal signalling axis via a glucocorticoid-driven transcriptional programme. We unraveled the physiological significance of this catabolic process using skeletal muscle-specific glucocorticoid receptor (GR) knockout (GRmKO) mice. These mice have increased muscle mass but smaller adipose tissues.
Metabolically, GRmKO mice show a drastic shift of energy utilization and storage in muscle, liver and adipose tissues. The resulting depletion of plasma alanine serves as a cue to increase plasma levels of FGF21 and activates liver-fat communication, leading to the activation of lipolytic genes in adipose tissues. This skeletal muscle-liver-fat signalling axis may serve as a target for the
development of therapies against various metabolic diseases, including obesity.
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| Free Research Field |
内分泌学
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